Descriptions of the regulation of blood volume often fail to consider the possibility of at least two different mechanisms controlling plasma volume and red cell mass, and the relative importance of these mechanisms over time. Short-term experiments (24 hours) in the fetal lamb have shown a change in plasma volume in response to different stresses (e.g., hemorrhage, hypoxia). No short-term responses of fetal red cell mass have been measured. The proposed study will examine the long-term mechanisms available to the fetal lamb for the maintenance of blood volume. Special consideration will be given to the regulation of fetal red cell mass. Experiments will be performed in chronically characterized fetal lambs over a period of three weeks to seven weeks (1) under control conditions, (2) in anephric fetuses, (3) during chronic hypoxia due to long-term reductions in fetal placental blood flow, (4) after an acute reduction in red cell mass (5) after a sustained reduction in red cell mass and (6) after a sustained increase in red mass. In addition, some fetal lambs will be ventilated in utero to study the effects of increased PO2 on fetal erythropoietin production. Finally, the rate of red blood cell production and destruction will be measured. Fetal red cell mass, plasma volume, hematocrit, blood pressures, maternal plasma osmolality, fetal urine production, urine osmolality, fetal plasma osmolality, urine production, urine osmolality and plasma hormone levels (catecholamines, plasma renin activity and erythropoietin) will be measured. Regulation of fetal blood volume is subject to constraints which do not exist in the adult. The proposed experiments will test the hypothesis that the differences between the adult and the fetus are due, in part, to the prevailing fetal oxygen tensions, the relative magnitude of fetal red cell turnover rate and the fetal growth rate. Additionally, a second hypothesis to be tested is that fetal long-tern responses to a reduction in red cell mass are different from the short-term responses.